Interferon-gamma-inducing oral vaccination with Leishmania amazonensis antigens protects BALB/c and C57BL/6 mice against cutaneous leishmaniasis

• Published in: Vaccine Vol. 21; no. 25-26; pp. 3534 - 3541
• Main Authors: Pinto, Eduardo Fonseca, de Mello Cortezia, Marcelle, Rossi-Bergmann, Bartira
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 08.09.2003; Elsevier; Elsevier Limited
• Subjects: Administration, Oral; Animals; Antigens; Antigens, Protozoan - immunology; Biological and medical sciences; Cutaneous leishmaniasis; Cytokines - biosynthesis; Depletion; Drug Hypersensitivity - immunology; Feasibility studies; Fundamental and applied biological sciences. Psychology; Hypersensitivity; Immunization; Immunological tolerance; Infections; Injections; Injections, Subcutaneous; Interferon; Interferon Inducers - pharmacology; Interferon-gamma - biosynthesis; Interleukin 10; Interleukin 4; Leishmania; Leishmania amazonensis; Leishmania mexicana - immunology; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - pathology; Leishmaniasis, Cutaneous - prevention & control; Liver - physiology; Lymph nodes; Lymph Nodes - metabolism; Lymphatic system; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mucosa; Nodes; Oral vaccine; Parasites; Parasitic diseases; Penicillin; Promastigotes; Protozoa; Protozoan Vaccines - administration & dosage; Protozoan Vaccines - adverse effects; Protozoan Vaccines - immunology; Receptors, Antigen, T-Cell, gamma-delta - immunology; Skin - pathology; T cell receptors; T-Lymphocytes - immunology; Tolerance; Tropical diseases; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vector-borne diseases; γ-Interferon; Brazil; United States > US; Tolerance; Leishmania; Oral vaccine; Kinetoplastida; Immunoprotection; Protozoa; Vaccination; Cytokine; Rodentia; Oral administration; Antigen; Immunoprophylaxis; Vertebrata; Mammalia; Mouse; Leishmania amazonensis; Gamma interferon
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(03)00427-4

The induction of oral tolerance against disease-inducing antigens has emerged as a feasible strategy to prevent immunopathologies. In this study, we investigated the effect of oral immunization with whole antigens of Leishmania amazonensis promastigotes (LaAg) on murine cutaneous leishmaniasis. We found that two oral doses with 100μg LaAg rendered BALB/c and C57BL/6 mice more resistant against subsequent infection with L. amazonensis. The oral vaccine also partially protected BALB/c mice against Leishmania major infection. Unlike the oral route, hepatic immunization was without effect, indicating a requirement for antigen passage through the gut mucosa. Oral LaAg significantly impaired the capacity of infected BALB/c mice to mount a disease-associated hypersensitivity response, compatible with peripheral tolerization. Both IFN-γ and IL-10, but not IL-4 were greatly elevated in the mesenteric lymph nodes whereas only IFN-γ was increased in the peripheral lymph nodes, compatible with a TH1 cytokine response. Gamma delta TCR+ T cells may be an important component in antigenic sensitization of the gut mucosa since their depletion during oral immunization reverted protection. These results demonstrate for the first time the feasibility of using the oral route of immunization to induce protection against cutaneous leishmaniasis using a crude parasite antigen.